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TRPM2: a calcium influx pathway regulated by oxidative stress and the novel second messenger ADP-ribose

Frank J P Kühn1, Inka Heiner, Andreas Lückhoff

  • 1Medical Faculty, RWTH Aachen, Institute of Physiology, Pauwelsstrasse 30, 52057 Aachen, Germany.

Pflugers Archiv : European Journal of Physiology
|June 14, 2005
PubMed

Insights

Transient Receptor Potential Melastatin 2 (TRPM2) channels are activated by ADP-ribose (ADPR) and calcium ions. This gating mechanism is crucial for cellular signaling, particularly in response to oxidative stress and inflammation.

Area of Science:

  • Molecular Biology
  • Ion Channel Physiology
  • Cell Signaling

Background:

  • Transient Receptor Potential (TRP) channels are a diverse family of cation channels.
  • TRP Melastatin 2 (TRPM2) channels possess a unique gating mechanism involving ADP-ribose (ADPR).
  • The intracellular C-terminal tail of TRPM2 shares homology with pyrophosphatase enzymes.

Purpose of the Study:

  • To review the gating properties of TRPM2 channels.
  • To elucidate proposed in vivo activation pathways of TRPM2.
  • To highlight the role of TRPM2 in various physiological and pathological conditions.

Main Methods:

  • Literature review of TRPM2 channel function.
  • Analysis of molecular interactions between ADPR, calcium, and TRPM2.
  • Examination of TRPM2's role in oxidative stress and other signaling pathways.

Main Results:

  • ADPR binding to the C-terminal tail of TRPM2 initiates channel gating.
  • Cytosolic calcium enhances ADPR-mediated TRPM2 gating, suggesting a calcium influx signaling system.
  • NAD, hydrogen peroxide (H2O2), and cyclic ADPR act as additional stimuli, potentially synergizing with ADPR.
  • H2O2 can induce ADPR formation in cellular compartments like the nucleus and mitochondria.

Conclusions:

  • TRPM2 channels are key mediators in cellular signaling pathways.
  • TRPM2 plays a significant role in cell death during oxidative stress and reperfusion injury.
  • TRPM2 is implicated in the pathogenesis of diabetes mellitus and leukocyte activation.

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